Characterizing Interactions Between Descending Cortical and Spinal Sensorimotor Circuits Across the Adult Lifespan and their Implications for Balance Control 公开

Lopez, Alejandro (Fall 2022)

Permanent URL: https://etd.library.emory.edu/concern/etds/2b88qd454?locale=zh
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Abstract

Successful balance performance remains a crucial prerequisite for human beings to safely navigate activities of daily living. However, deficits in balance ability across the human lifespan remain important intrinsic factors for increased risk of falls. The aging process can substantially contribute to poor balance function due to changes in underlying neural circuitry. Human sensorimotor circuits in the cortex and spinal cord have been evaluated using non-invasive stimulation techniques to characterize their physiological function and connectivity. Yet, the complex interactions between cortical and spinal sensorimotor circuits across the adult lifespan and their relation to successful balance control remain poorly understood. To advance our understanding of balance control in humans, the use of non-invasive paired stimulation paradigms has enabled novel insights into interactions between descending cortical and spinal sensorimotor circuits. This dissertation investigates the neurophysiological correlates of balance control by characterizing interactions between descending cortical and spinal sensorimotor circuits across the adult lifespan. In Study 1, we replicated previous research that has demonstrated the ability of descending cortical circuits to modulate the excitability of spinal reflexes; however, our results revealed that modulation occurred throughout the physiological recruitment order of spinal reflexes and descending cortical influences contributed to changing the reflex gain in healthy adults. These findings can inform future studies investigating neurophysiologic processes that modulate recruitment order and reflex gain in conditions of abnormal balance control. Additionally, in Study 2, we examined the relative timing of converging descending cortical inputs with respect to ascending afferent inputs within the spinal cord. While standardized timing between converging inputs resulted in significant descending modulation of spinal reflexes, individual-specific timing between inputs resulted in significantly greater descending modulation of spinal reflexes. These findings suggest that using individual-specific stimulation parameters when measuring descending modulation of spinal reflexes can inform future studies on the complex array of connections between descending cortical and spinal sensorimotor circuits. Finally, in Study 3, we investigated the effects of aging-related changes and task-related activation on descending modulation of spinal reflexes. We demonstrated that task-related activation resulted in differential modulation of spinal reflexes via direct and indirect descending circuits, and aging resulted in greater descending inhibitory control of spinal reflexes during task-related activation. Taken together, our results suggest that descending cortical and spinal sensorimotor circuits have differentially important roles throughout the adult lifespan in the regulation of spinal circuit activity, and these interactions remain highly implicated in the neural control of balance ability.

Table of Contents

Table of Contents

CHAPTER 1: GENERAL INTRODUCTION 1

1.1 INTRODUCTION 2

1.2 NEURAL CIRCUITS IMPLICATED IN BALANCE 4

1.2.1 The spinal reflex pathway 4

1.2.2 Descending cortical and subcortical pathways 6

1.3 INFLUENCE OF DESCENDING PATHWAYS ON SPINAL REFLEXES 8

1.3.1 Paired non-invasive stimulation to probe sensorimotor integration within the spinal cord 8

1.4 GAP IN KNOWLEDGE 10

1.5 DISSERTATION OVERVIEW 11

 

CHAPTER 2: INTEGRATION OF CONVERGENT SENSORIMOTOR INPUTS WITHIN SPINAL REFLEX CIRCUITS IN HEALTHY ADULTS 13

2.1 ABSTRACT 14

2.2 INTRODUCTION 15

2.3 METHODS 19

2.3.1 Study participants 19

2.3.2 Experimental design 19

2.3.3 Electromyography (EMG) procedures 20

2.3.4 Unconditioned soleus H-reflex recruitment curve 20

2.3.5 Transcranial magnetic stimulation (TMS) procedures 22

2.3.6 TMS-conditioned H-reflex recruitment curves 23

2.3.7 Calculation of H-reflex and M-response amplitude, Hmax, and Mmax 23

2.3.8 Determination of magnitude of TMS-induced facilitation 24

2.3.9 Statistical analyses 24

2.4 RESULTS 26

2.4.1 Demonstration of short- and long-interval facilitation of H-reflexes at a single PNS intensity (20% Mmax) 26

2.4.2 Evaluation of short- and long-interval facilitation of H-reflexes at a range of PNS intensities 27

2.4.3 Comparison of unconditioned and conditioned Hmax and intensity required to elicit Hmax 29

2.5 DISCUSSION 30

2.5.1 Study limitations 35

2.6 CONCLUSIONS 37

 

CHAPTER 3: TEMPORAL PROFILE OF DESCENDING CORTICAL MODULATION OF SPINAL EXCITABILITY: GROUP AND INDIVIDUAL-SPECIFIC EFFECTS 38

3.1 ABSTRACT 39

3.2 INTRODUCTION 40

3.3 METHODS 44

3.3.1 Study participants 44

3.3.2 Experimental design 44

3.3.3 Electromyographic recordings 45

3.3.4 Peripheral nerve stimulation 46

3.3.5 Transcranial magnetic stimulation 47

3.3.6 TMS-conditioning of the soleus H-reflex 47

3.3.7 Data processing 48

3.3.8 Statistical procedures 49

3.4 RESULTS 50

3.4.1 Identification the earliest onset of H-reflex facilitation in individual participants 50

3.4.2 Influence of ISI on TMS-conditioning of H-reflex facilitation 52

3.4.3 Comparison of early and late facilitation measured at individualized ISI versus standard ISI 53

3.5 DISCUSSION 54

3.5.1 Mechanisms and interpretation of earliest onset of facilitation 55

3.5.2 Mechanisms and interpretation of longer-interval and maximal facilitation 57

3.5.3 Potential mechanisms and implications of inter-individual variability in magnitude and timing of TMS-induced facilitation 60

3.5.4 Limitations and future directions 61

3.6 CONCLUSIONS 63

 

CHAPTER 4: INFLUENCE OF AGE AND TASK-RELATED ACTIVATION ON DESCENDING CORTICAL MODULATION OF SPINAL SENSORIMOTOR CIRCUITRY 64

4.1 ABSTRACT 65

4.2 INTRODUCTION 66

4.3 METHODS 70

4.3.1 Study participants 70

4.3.2 Experimental design 71

4.3.3 Electromyography (EMG) procedures 71

4.3.4 Peripheral nerve stimulation (PNS) procedures 72

4.3.5 Transcranial magnetic stimulation (TMS) procedures 73

4.3.6 TMS-conditioning of soleus H-reflexes 74

4.3.7 Beam-walking task 75

4.3.8 Statistical analyses 76

4.4 RESULTS 77

4.4.1 Effects of task-related activation and aging on unconditioned soleus H-reflexes 77

4.4.2 Effects of timing and aging on TMS-conditioned soleus H-reflexes at rest 78

4.4.3 Effects of task-related activation and aging on TMS-conditioned soleus H-reflexes 79

4.4.4 Change in conditioned H-reflex % between task-related activation and timing 82

4.4.5 Walking balance performance and the relation to descending modulation of spinal reflexes 83

4.5 DISCUSSION 84

4.5.1 Task- and aging-related changes in unconditioned soleus H-reflexes 85

4.5.2 Mechanisms and interpretation of task-related changes in TMS-conditioned soleus H-reflexes 86

4.5.3 Mechanisms and interpretation of aging-related changes in TMS-conditioned soleus H-reflexes 88

4.5.4 Implications for future research studies 90

4.5.5 Study limitations 91

4.6 CONCLUSIONS 92

 

CHAPTER 5: DISCUSSION, CONCLUSIONS, AND FUTURE DIRECTIONS 93

5.1 SUMMARY OF RESULTS 94

5.2 CONSIDERATIONS AND SUGGESTIONS FOR FUTURE STUDIES 96

5.3 IMPLICATIONS FOR CLINICAL TRANSLATION 100

5.4 LIMITATIONS 101

5.5 CONCLUSIONS 105

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